Rapid detection of a recombinant hotspot associated with Charcot-Marie-Tooth disease type IA duplication by a PCR-based DNA test.
A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. We developed a PCR-based diagnostic method to detect a recombination hotspot associated with the CMT1A duplication. Thirty-one CMT1A Chinese patients from different families and 50 healthy people over 65 years of age were studied. Twenty-seven of the 31 cases demonstrated the 3.2-kb hotspot crossover, of which there were two subgroups. The type 1 crossover breakpoint was located at the distal CMT1A-REP around the PmeI site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot crossover in CMT1A duplication patients. The type 2 crossover breakpoint was located at the distal CMT1A-REP around the base 3625 region, accounting for 3 of the 27 cases. The results correlated very well with the results of Southern transfer analysis. This study has a potentially important role in the diagnosis of CMT1A disease.
Chang
J G
JG
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. f1037437@ms8.hinet.net
Jong
Y J
YJ
Wang
W P
WP
Wang
J C
JC
Hu
C J
CJ
Lo
M C
MC
Chang
C P
CP
D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D002681:China; D019457:Chromosome Breakage / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011995:Recombination, Genetic / Q000235:genetics